Environmental enrichment and physical exercise prevent stress-induced social avoidance and blood-brain barrier alterations via Fgf2
Abstract
Abstract Chronic stress promotes blood-brain barrier (BBB) integrity loss leading to passage of inflammatory mediators in mood-regulating brain areas and establishment of depressive behaviors. Conversely, neurovascular adaptations favoring stress resilience and preventive strategies to promote them are undetermined. We report that environmental enrichment dampens stress-induced loss of endothelial tight junction Claudin-5 (Cldn5) along with anxiety- and depression-like behaviors in male mice via an increase in fibroblast growth factor 2 (Fgf2). Coping with voluntary physical exercise also protects the BBB from stress deleterious effects by increasing Fgf2. Fgf2 is mostly expressed by glial cells, and viral-mediated astrocyte-specific Fgf2 upregulation prevents stress-induced social avoidance while downregulation increases stress susceptibility and blunts physical exercise benefits. Treatment of mouse and human endothelial cells with Fgf2 prior an immune challenge reduces BBB dysfunction, Cldn5 loss, and altered signaling supporting its protective role. Circulating FGF2 level is linked with depression severity and symptomatology in men and women reinforcing involvement of this growth factor in mood disorders.
Article Details
Authors (54)
Sam E. J. Paton
José L. Solano
Alice Cadoret
Adeline Collignon
Luisa Bandeira Binder
Béatrice Daigle
Laura Menegatti Bevilacqua
Émanuelle Richer
François Coulombe-Rozon
Laurence Dion-Albert
Katarzyna A. Dudek
Philippe Beauchamp-Kerr
Felix-Antoine Berube
Janick Boissonneault
Francois Borgeat
Lionel Cailhol
Pierre David
Simon Ducharme
Alexandre Dumais
Helen Findlay
Stéphane Guay
Steve Geoffrion
Charles-Édouard Giguère
Roger Godbout
Alexandre Hudon
Robert-Paul Juster
Real Labelle
Marc Lavoie
Myriam Lemyre
Alain Lesage
Cécile Le Page
Olivier Lipp
Sonia Lupien
Jean-Pierre Melun
Marie-France Marin
Carolle Marullo
Francois Noel
Jean-Francois Pelletier
Vincent Tascherau-Dumouchel
Pierrich Plusquellec
Stéphane Potvin
Ahmed-Jérome Romain
Marc Sasseville
Daniel St-Laurent
Manuel Serrano
Emmanuel Stip
Christo Todorov
Valerie Tourjman
Samir Taga
Claudia Trudel-Fitzgerald
Martha Francoise Ulysse
Andreas Ziegenhorn
Manon Lebel
Caroline Ménard